Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein

Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA. Electronic address: .
FEBS letters (Impact Factor: 3.17). 09/2012; 586(21). DOI: 10.1016/j.febslet.2012.09.015
Source: PubMed


Aminoacylase 3 (AA3) mediates deacetylation of N-acetyl aromatic amino acids and mercapturic acids. Deacetylation of mercapturic acids of exo- and endobiotics are likely involved in their toxicity. AA3 is predominantly expressed in kidney, and to a lesser extent in liver, brain, and blood. AA3 has been recently reported to interact with the hepatitis C virus core protein (HCVCP) in the yeast two-hybrid system. Here we demonstrate that AA3 directly binds to HCVCP (K(d) ∼10μM) that may by implicated in HCV pathogenesis. AA3 also revealed a weak endopeptidase activity towards the N-terminus of HCVCP. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: AA3cleavesHCVCP by protease assay (View interaction). AA3cleavesAA3 by protease assay (View interaction). AA3binds to HCVCP by surface plasmon resonance (View Interaction:1,2,3,4,5).

Download full-text


Available from: Kirill Tsirulnikov, Feb 18, 2015
  • Source
    • "associated factor 9 73 000 Nedialkov & Triezenberg, 2004 Transcription factor TFIIA nd Transcription factor TFIIB 3000 Swi1and Snf5 subunits of the chromatin remodeling complex nd Ferreira et al., 2005 Exonuclease UL12 DNA double-strand break-sensing complex 31.1 Balasubramanian et al., 2010 Hepatitis viruses Core protein Microtubulin 75–100 Roohvand et al., 2009 Nucleophosmin-1 2510 Lee et al., 2009 Aminoacylase 3 10 100 Tsirulnikov et al., 2012 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Despite decades of antiviral drug research and development, viruses still remain a top global healthcare problem. Compared to eukaryotic cells, viruses are composed by a limited numbers of proteins that, nevertheless, set up multiple interactions with cellular components, allowing the virus to take control of the infected cell. Each virus/host interaction can be considered as a therapeutical target for new antiviral drugs but, unfortunately, the systematic study of a so huge number of interactions is time-consuming and expensive, calling for models overcoming these drawbacks. Surface plasmon resonance (SPR) is a label-free optical technique to study biomolecular interactions in real time by detecting reflected light from a prism-gold film interface. Launched 20 years ago, SPR has become a nearly irreplaceable technology for the study of biomolecular interactions. Accordingly, SPR is increasingly used in the field of virology, spanning from the study of biological interactions to the identification of putative antiviral drugs. From the literature available, SPR emerges as an ideal link between conventional biological experimentation and system biology studies functional to the identification of highly connected viral or host proteins that act as nodal points in virus life cycle and thus considerable as therapeutical targets for the development of innovative antiviral strategies.
    Full-text · Article · Sep 2013 · Critical Reviews in Microbiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early life stage mortality is an important issue for Atlantic cod aquaculture, yet the impact of the cod maternal (egg) transcriptome on egg quality and mortality during embryonic development is poorly understood. In the present work, we studied embryonic mortality and maternal transcript expression using eggs from 15 females. Total mortality at 7days post-fertilization (7 dpf, segmentation stage) was used as an indice of egg quality. A 20,000 probe (20K) microarray experiment compared the 7hours post-fertilization (7 hpf, ~2-cell stage) egg transcriptome of the two lowest quality females (>90% mortality at 7 dpf) to that of the highest quality female (~16% mortality at 7 dpf). Forty-three microarray probes were consistently differentially expressed in both low versus high quality egg comparisons (25 higher expressed in low quality eggs, and 18 higher expressed in high quality eggs). The microarray experiment also identified many immune-relevant genes [e.g. interferon (IFN) pathway genes ifngr1 and ifrd1)] that were highly expressed in eggs of all 3 females regardless of quality. Twelve of the 43 candidate egg quality-associated genes, and ifngr1, ifrd1 and irf7, were included in a qPCR study with 7 hpf eggs from all 15 females. Then, the genes that were confirmed by qPCR to be greater than 2-fold differentially expressed between 7 hpf eggs from the lowest and highest quality females (dcbld1, ddc, and acy3 more highly expressed in the 2 lowest quality females; kpna7 and hacd1 more highly expressed in the highest quality female), and the 3 IFN pathway genes, were included in a second qPCR study with unfertilized eggs. While some maternal transcripts included in these qPCR studies were associated with extremes in egg quality, there was little correlation between egg quality and gene expression when all females were considered. Both dcbld1 and ddc showed greater than 100-fold differences in transcript expression between females and were potentially influenced by family. The Atlantic cod ddc (dopa decarboxylase) complete cDNA was characterized, and has a 1461bp open reading frame encoding a 486 amino acid protein that contains all eight residues of the conserved pyridoxal 5'-phosphate binding site including the catalytic lysine. This study provides valuable new information and resources related to the Atlantic cod egg transcriptome. Some of these microarray-identified, qPCR-confirmed, Atlantic cod egg transcripts (e.g. ddc, kpna7) play important roles during embryonic development of other vertebrate species, and may play similar functions in Atlantic cod.
    Full-text · Article · May 2014 · Marine Genomics